Monofluorophosphates

A number of salts of the monofluoro- and hexafluorophosphoric acids are known and some are commercially important. The salts of difluorophosphoric acid are typically less stable toward hydrolysis and are less well characterized. Sodium monofluorophosphate [7631-97-2] the most widely used dentifrice additive for the reduction of tooth decay, is best known (see Dentifrices). Several hexafluorophosphates can be prepared by neutralization of the appropriate base using hexafluorophosphoric acid. The monofluorophosphates are usually prepared by other methods (57) because neutralization of the acid usually results in extensive hydrolysis. 

Monofluorophosphates. Monofluorophosphates are probably the best characterized series of fluoroxy salts. The PO F ion is stable ia neutral or slightly alkaline solution. The alkaU metal and ammonium monofluorophosphates are soluble ia water but the alkaline-earth salts are only slightly soluble, eg, CaPO F is not water-soluble and precipitates as the dihydrate. 

Monofluorophosphates of ammonium, lithium, sodium, potassium, silver, calcium, strontium, barium, mercury, lead, and benzidine have been described (70) as have the nickel, cobalt, and ziac salts (71), and the cadmium, manganese, chromium, and iron monofluorophosphates (72). Many of the monofluorophosphates are similar to the corresponding sulfates (73). 

The monofluorophosphates can be prepared by neutralization of monofluorophosphoric acid (1). Sodium monofluorophosphate [7631 -97-2] is prepared commercially (57) by fusion of sodium fluoride and sodium metaphosphate, and the potassium monofluorophosphate [14104-28-0] can be prepared similarly. Insoluble monofluorophosphates can be readily prepared from reaction of nitrate or chloride solutions with sodium monofluorophosphate. Some salts are prepared by metathetical reactions between silver monofluorophosphate [66904-72-1] and metal chlorides. 

Molten alkah metal monofluorophosphates are reactive and corrosive, hydrolyzing to generate HF and reacting with many metals and ceramics. 

They readily dissolve metal oxides and are effective metal surface cleaners and fluxes (see Metal surface treatments). They also have bactericidal and fungicidal properties (74). However, the main commercial appHcation among monofluorophosphates is of sodium monofluorophosphate ia dentifrices. 

Sodium monofluorophosphate, mp 625°C, is soluble ia water to the extent of 42 g/100 g solution. The pH of a 2% solution is between 6.5 and 8.0. Dilute solutions are stable indefinitely ia the absence of acid or cations that form iasoluble fluorides. 

Sodium monofluorophosphate is used ia most dentifrices at a concentration of 0.76 wt % which produces the desired fluoride level of 1000 ppm although one extra strength dentifrice has 1.14 wt % and 1500 ppm F. Although the mechanism of its efficacy ia reducing dental decay is not completely understood (75), it almost certainly reacts with the apatite of the tooth converting it to fluoroapatite which is less soluble ia mouth acids (see Dentifrices). 

The JnitedSfates Pharmacopeia (76) specifications for sodium monofluorophosphate require a minimum of 12.1% fluoride as PO F (theoretical 13.2%) and a maximum of 1.2% fluoride ion reflecting unreacted sodium fluoride. Analysis for PO F is by difference between total fluoride ia the product less fluoride ion as determined by a specific ion electrode. The oral LD q of sodium monofluorophosphate ia rats is 888 mg/kg. 

Eluoride added to a compatible dentifrice base at a level of 1000 ppm has been clinically proven to reduce the incidence of dental caries by about 25% on average, even in areas where the water supply is fluoridated (4). Elevation to 1500 ppm increases the protection. Sources of fluoride approved for use in dentifrices are sodium fluoride [7681-49-4] (0.22%), sodium monofluorophosphate (0.76%), and stannous fluoride [7783-47-3] (0.41%). The Eood and Dmg Administration regulates fluoridated dentifrices as dmgs and has estabUshed parameters for safe and effective products. CompatibiUty of the fluoride with the abrasive is an important requirement. 

The active part of the molecule is the fluoride ion, which is why two other fluorine-containing compounds, sodium fluoride and sodium monofluorophosphate, are also used. 

Stannous fluoride can be used with abrasives that contain calcium, which prevents sodium fluoride from being effective. Sodium monofluorophosphate was developed to avoid infringing on the Crest patent. 

For the preparation of monofluorophosphates there are quite a lot of methods found in literature. The alkali salts are obtained by shortly melting poly- or trimetaphosphate with alkali fluoride (29,30) - the application of graphite vessels yielding particulary pure products (31) ... 

Up to know crystal structure analyses have been made with difluorophosphates, monofluorophosphates and dichlorophosphates only. Table 3 gives the bond lengths and bond angles in these three halophosphates. 

Looking at the crystal structures of the monofluorophosphates, it is surprising, that the three PO bonds are of different lengths. These differences are out of the limits of error at least in case of the very exactly calculated data of Ca[P03F] 2 H2O and (NH4)2[P03F] H2O (26) (see Table 3). In fact this leads to a Cj symmetry for the POgF ion. 

Figure 10 Capillary ion analysis of 30 anions 1 = thiosulfate, 2 = bromide, 3 = chloride, 4 = sulfate, 5 = nitrite, 6 = nitrate, 7 = molybdate, 8 = azide, 9 = tungstate, 10 = monofluorophosphate, 11 = chlorate, 12 = citrate, 13 = fluoride, 14 = formate, 15 = phosphate, 16 = phosphite, 17 = chlorite, 18 = galactarate, 19 = carbonate, 20 = acetate, 21 = ethanesulphonate, 22 = propionate, 23 = propanesulphonate, 24 = butyrate, 25 = butanesulphonate, 26 = valerate, 27 = benzoate, 28 = D-glutamate, 29 = pentane-sulphonate and 30 = D-gluconate. Experimental conditions fused silica capillary, 60 cm (Ld 52 cm) x 50 p i.d., voltage 30 kV, indirect UV detection at 254 nm, 5 mM chromate, 0.5 mM NICE-Pak OFM Anion-BT, adjusted to pH 8.0, with 100 mM NaOH. (From Jones, W. R. and Jandik, R, /. Chromatogr., 546, 445,1991. With permission.)...

Daily doses studied have ranged from 9 to 22.6 mg of fluoride over time periods of 1-4 years [98]. These trials were particularly concerned with the use of slow-release NaF [112,113] or sodium monofluorophosphate preparations [114,115], and they generally led to reductions in the incidence of bone fracture, as shown in Table 3. In addition, they typically caused increased bone density at the neck of the femur, the femoral condyle and the lower spine [98] (Table 3). 

This approach may not account for all the fluoride released by glass-ionomers [252], A recent study has used two methods of decomplexation of fluoride, using the same solutions for both methods, by dividing a given storage volume into two and treating each aliquot differently. One aliquot was diluted with an equal volume of TISAB, as is usual in the determination of fluoride by ion-selective electrode. The other solution was treated with a small volume of 4 M hydrochloric acid, allowed to stand for 3 h, then neutralised with an equal amount of 4 M sodium hydroxide. A volume of TISAB equal to the initial volume of the aliquot was added. This technique is known to liberate fluoride from monofluorophosphate as well as from aluminofluoride complexes [253],... 

Resin-modified glass-ionomers, like their conventional counterparts, are capable of releasing fluoride [224,264,265], and in greater amounts under acid conditions than neutral ones [265], Release rates and release profiles have been shown to be comparable with those from conventional glass-ionomer cements [264,265], Other ions have also been shown to be released by these materials and, as for fluoride, these ions show a greater release under low pH conditions [265], However, the level of phosphorus released has been shown to be much lower from resin-modified glass-ionomers than from conventional ones [263], This suggests that there is little or no possibility of association of fluoride as monofluorophosphate, but rather that almost all of the fluoride is released either as the free fluoride ion or as alumino-fluoride complex ions. 

G. Silverman, The sensitivity reducing effect of brushing with a potassium nitrate-sodium monofluorophosphate dentifrice, Compend. Contin. Educ. Dent. 6 (1985) 131-133. 

J.L. Sebert, P. Richard, I. Mennecier, J.P. Bisset, G. Loeb, Monofluorophosphate increases lumbar bone density in osteopenic patients A double-masked randomized study, Osteoporos. Int. 5 (1995) 108-114. 

J.Y. Reginster, L. Meurmans, B. Zegels, C. Gossete, The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. A randomized, controlled trial, Ann. Intern. Med. 

J.D. Ringe, A. Dorst, C. Kipshoeven, L.C. Rovati, I. Setnikar, Avoidance of vertebral fractures in men with idiopathic osteoporosis by a three year therapy with calcium and low-dose intermittent monofluorophosphate, Osteoporos. Int. 8 (1998) 47-52. 

R.W. Billington, J.A. Williams, A. Dorban, G.J. Pearson, Glass ionomer cement Evidence pointing to fluorine release in the form of monofluorophosphate in addition to fluoride ion. Biomaterials 25 (2004) 3399-3402. 

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